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Antibiotics (Basel, Switzerland) Apr 2024Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We...
Central nervous system (CNS) lesions, especially invasive fungal diseases (IFDs), in immunocompromised patients pose a great challenge in diagnosis and treatment. We report the case of a 48-year-old man with acute myeloid leukaemia and probable pulmonary aspergillosis, who developed hyposthenia of the left upper limb, after achieving leukaemia remission and while on voriconazole. Magnetic resonance imaging (MRI) showed oedematous CNS lesions with a haemorrhagic component in the right hemisphere with lepto-meningitis. After 2 weeks of antibiotics and amphotericin-B, brain biopsy revealed chronic inflammation with abscess and necrosis, while cultures were negative. Clinical recovery was attained, he was discharged on isavuconazole and allogeneic transplant was postponed, introducing azacitidine as a maintenance therapy. After initial improvement, MRI worsened; brain biopsy was repeated, showing similar histology; and 16S metagenomics sequencing analysis was positive (, ). Despite 1 month of meropenem, MRI did not improve. The computer tomography and PET scan excluded extra-cranial infectious-inflammatory sites, and auto-immune genesis (sarcoidosis, histiocytosis, CNS vasculitis) was deemed unlikely due to the histological findings and unilateral lesions. We hypothesised possible IFD with peri-lesion inflammation and methyl-prednisolone was successfully introduced. Steroid tapering is ongoing and isavuconazole discontinuation is planned with close follow-up. In conclusion, the management of CNS complications in immunocompromised patients needs an interdisciplinary approach.
PubMed: 38786116
DOI: 10.3390/antibiotics13050387 -
Annals of Clinical Microbiology and... May 2024The population structure and the correlation between antimicrobial resistance (AMR) phenotypes and genotypes in Aeromonas species isolated from patients with...
BACKGROUND
The population structure and the correlation between antimicrobial resistance (AMR) phenotypes and genotypes in Aeromonas species isolated from patients with gastroenteritis are not well understood. The aims of the study were to: (1) investigate the antimicrobial susceptibility profiles of Aeromonas species isolated from patients with gastroenteritis; (2) explore the relationship between AMR genes and resistance phenotypes; and (3) describe the population structure of these isolates and provide evidence of transmission events among them.
METHODS
This microbiological survey was performed at the Microbiology Laboratory of the Emek Medical Center in Afula, Israel. Cultivation of Aeromonas was attempted from stool samples that tested positive by PCR. Antimicrobial susceptibility testing (AST) was performed using the Sensititre GN3F microdilution panel. Whole genome sequencing (WGS) was done using the Illumina NextSeq500/550 system. Phylogenetic studies involved multi-locus sequence typing (MLST) and core genome (cg) MLST. Resistance mechanisms were identified using the Comprehensive Antibiotic Resistance Database and compared with the AST results.
RESULTS
The study included 67 patient-unique isolates. The species that were identified included A. caviae (n = 58), A. dhakensis (n = 3), A. media (n = 2), A. veronii (n = 2) and A. hydrophila (n = 2). Isolates were almost uniformly susceptible to amikacin, gentamicin, aztreonam, cefepime, ceftazidime, ciprofloxacin and meropenem. All isolates with the exception of 1-2 isolates were resistant to ampicillin, cefazolin and ampicillin-sulbactam which was compatible with the presence of the bla genes. Variable resistance rates were observed to cefuroxime, cefoxitin, ceftriaxone, piperacillin-tazobactam that were not correlated with the presence of other β-lactamase genes. Resistance to tetracycline and trimethoprim-sulfamethoxazole correlated with the presence of tetA and sul1, respectively. The population structure of A. caviae was highly diverse with the minority of the isolates (16/57) clustering into six defined sequence types. A cgMLST-based distance of four genes was found in one pair of isolates, suggesting common source transmission.
CONCLUSIONS
A. caviae is the dominant species related to gastroenteritis and is characterized by a diverse population structure, with almost no evidence for common-source transmission. Resistance rates to most antimicrobial agents were low and partially matched with the presence of resistance genes.
Topics: Humans; Gastroenteritis; Aeromonas; Microbial Sensitivity Tests; Anti-Bacterial Agents; Genotype; Phylogeny; Gram-Negative Bacterial Infections; Whole Genome Sequencing; Multilocus Sequence Typing; Child; Phenotype; Adult; Feces; Child, Preschool; Female; Male; Middle Aged; Drug Resistance, Bacterial; Israel; Aged; Infant; Adolescent; Young Adult; Drug Resistance, Multiple, Bacterial
PubMed: 38783344
DOI: 10.1186/s12941-024-00706-2 -
Antimicrobial Agents and Chemotherapy May 2024CERTAIN-1 was a Phase 3, double-blind, randomized, parallel group study of the efficacy and safety of cefepime-taniborbactam versus meropenem in the treatment of adults...
Patient outcomes by baseline pathogen resistance phenotype and genotype in CERTAIN-1, a Phase 3 study of cefepime-taniborbactam versus meropenem in adults with complicated urinary tract infection.
UNLABELLED
CERTAIN-1 was a Phase 3, double-blind, randomized, parallel group study of the efficacy and safety of cefepime-taniborbactam versus meropenem in the treatment of adults with complicated urinary tract infection (cUTI), including acute pyelonephritis. We determined susceptibility of Enterobacterales and baseline pathogens to cefepime-taniborbactam and comparators and characterized β-lactam resistance mechanisms. Microbiologic response and clinical response were assessed in patient subsets defined by baseline pathogens that were of cefepime-, multidrug-, or carbapenem-resistant phenotype or that carried β-lactamase genes. Among Enterobacterales baseline pathogens, 26.8%, 4.1%, and 3.0% carried genes for extended-spectrum β-lactamases (ESBLs), AmpC, and carbapenemases, respectively. Within each treatment group, while composite success rates at Test of Cure in resistant subsets by pathogen species were similar to those by pathogen overall, composite success rates in meropenem patients were numerically lower for cefepime-resistant (9/19; 47.4%) and ESBL (13/25; 52.0%) compared with overall (62/100; 62.0%). Cefepime-taniborbactam achieved composite success in 7/8 (87.5%) patients with carbapenem-resistant Enterobacterales and 8/9 (88.9%) patients with Enterobacterales with a carbapenemase gene (5 OXA-48-group; 2 KPC-3; 2 NDM-1). Cefepime-taniborbactam also achieved composite success in 8/16 (50.0%) patients and clinical success in 13/16 (81.3%) patients with ; corresponding rates were 4/7 (57.1%) and 6/7 (85.7%) for meropenem. Cefepime-taniborbactam demonstrated efficacy in adult cUTI patients with cefepime-, multidrug-, and carbapenem-resistant pathogens including pathogens with ESBL, AmpC, and carbapenemase genes.
CLINICAL TRIALS
This study is registered with ClinicalTrials.gov as NCT03840148.
PubMed: 38780262
DOI: 10.1128/aac.00236-24 -
Journal of Global Antimicrobial... May 2024Enterococcus faecium (E. faecium) stands as a prominent pathogen contributing to Gram-positive bacterial infections in individuals who have undergone liver...
BACKGROUND
Enterococcus faecium (E. faecium) stands as a prominent pathogen contributing to Gram-positive bacterial infections in individuals who have undergone liver transplantation.
CASE PRESENTATION
A 66-year-old male with a three-year history of treated anxiety disorder was admitted to our hospital due to recurrent abdominal distension and oliguria. He was diagnosed with hepatic veno-occlusive disease (HVOD), hepatic failure, pneumonia, renal insufficiency and abdominal ascites. A liver transplantation procedure was performed, but the patient's infection index increased on the first day after surgery. Empirical antibiotic therapy with ceftriaxone and meropenem and preventive antifungal therapy were applied. Sputum culture, blood culture, ascites culture and bronchoalveolar lavage fluid (BALF) next-generation sequencing (NGS), revealed the presence of E. faecium. Given the application of various nephrotoxic immunosuppressive agents after liver transplantation, pre-existing renal insufficiency, severe bone marrow suppression, and a history of anxiety disorder treated with sertraline, contezolid was added for the treatment of the Gram-positive bacterial infection. Sixteen days after surgery, cultures from ascites and sputum yielded negative results for fungi and bacteria. Contezolid was subsequently discontinued without any reported adverse events during follow-up.
CONCLUSION
Treatment with contezolid as the first-line therapy for sepsis and pneumonia caused by E. faecium following liver transplantation has shown satisfactory efficacy and safety. Therefore, contezolid may hold great promise for managing this life-threatening condition.
PubMed: 38777179
DOI: 10.1016/j.jgar.2024.05.005 -
Open Forum Infectious Diseases May 2024Sepsis is a major cause of morbidity and mortality worldwide. When selecting empiric antibiotics for sepsis, clinicians are encouraged to use local resistance rates, but...
BACKGROUND
Sepsis is a major cause of morbidity and mortality worldwide. When selecting empiric antibiotics for sepsis, clinicians are encouraged to use local resistance rates, but their impact on individual outcomes is unknown. Improved methods to predict outcomes are needed to optimize treatment selection and improve antibiotic stewardship.
METHODS
We expanded on a previously developed theoretical model to estimate the excess risk of death in gram-negative bacilli (GNB) sepsis due to discordant antibiotics using 3 factors: the prevalence of GNB in sepsis, the rate of antibiotic resistance in GNB, and the mortality difference between discordant and concordant antibiotic treatments. We focused on ceftriaxone, cefepime, and meropenem as the anti-GNB treatment backbone in sepsis, pneumonia, and urinary tract infections. We analyzed both publicly available data and data from a large urban hospital.
RESULTS
Publicly available data were weighted toward culture-positive cases. Excess risk of death with discordant antibiotics was highest in septic shock and pneumonia. In septic shock, excess risk of death was 4.53% (95% confidence interval [CI], 4.04%-5.01%), 0.6% (95% CI, .55%-.66%), and 0.19% (95% CI, .16%-.21%) when considering resistance to ceftriaxone, cefepime, and meropenem, respectively. Results were similar in pneumonia. Local data, which included culture-negative cases, showed an excess risk of death in septic shock of 0.75% (95% CI, .57%-.93%) for treatment with discordant antibiotics in ceftriaxone-resistant infections and 0.18% (95% CI, .16%-.21%) for cefepime-resistant infections.
CONCLUSIONS
Estimating the excess risk of death for specific sepsis phenotypes in the context of local resistance rates, rather than relying on population resistance data, may be more informative in deciding empiric antibiotics in GNB infections.
PubMed: 38770211
DOI: 10.1093/ofid/ofae219 -
Journal of Global Antimicrobial... May 2024Acinetobacter pittii has emerged as an opportunistic nosocomial pathogen associated with hospital-acquired infections. The purpose of this study was to investigate the...
BACKGROUND
Acinetobacter pittii has emerged as an opportunistic nosocomial pathogen associated with hospital-acquired infections. The purpose of this study was to investigate the genetic structures of plasmids carrying carbapenemase genes bla and bla in A. pittii strains AR3676 and AR3651 isolated from patients.
METHODS
Antimicrobial susceptibility testing was performed using broth microdilution. Whole-genome sequencing and bioinformatics analysis were performed to characterize the genome of A. pittii AR3676 and AR3651. Conjugation experiments were conducted to evaluate plasmids transferability. Phylogenetic and comparative genomic analysis were performed to explore the characteristics of carbapenem-resistant A. pittii isolates worldwide.
RESULTS
The AR3676 strain exhibited resistance to imipenem. The 19,700-bp plasmid pAR3676-OXA-58 harbored bla with genetic contexts consisting of a truncated ISAba3-like-bla-ISAba3. Additionally, the AR3651 strain exhibited resistance to imipenem and meropenem. The genome of AR3651 comprised one 9,837-bp RepA_AB plasmid pAR3651-OXA-72 harboring bla. The bla was flanked by XerC/XerD recombination sites. The conjugation of plasmids pAR3676-OXA-58 and pAR3651-OXA-72 from A. pittii to A. baumannii ATCC 17978RIF failed three independent times. Phylogenetic analysis of A. pittii strains AR3676, AR3651 and other 504 A. pittii strains collected between 1966 and 2022 from various geographic localities, revealed genetic diversity with a heterogeneous distribution of carbapenemase genes.
CONCLUSION
A. pittii strains with plasmid carrying bla or bla may serve as an important reservoir of carbepenemase genes. The carbepenemase genes on a single plasmid may facilitate their dissemination and persistence. Additionally, the pdif sites and mobile elements play an important role in the mobilization of resistance genes and plasmid evolution.
PubMed: 38768708
DOI: 10.1016/j.jgar.2024.05.007 -
BMC Infectious Diseases May 2024The study aims were to evaluate the species distribution and antimicrobial resistance profile of Gram-negative pathogens isolated from specimens of intra-abdominal...
BACKGROUND
The study aims were to evaluate the species distribution and antimicrobial resistance profile of Gram-negative pathogens isolated from specimens of intra-abdominal infections (IAI), urinary tract infections (UTI), respiratory tract infections (RTI), and blood stream infections (BSI) in emergency departments (EDs) in China.
METHODS
From 2016 to 2019, 656 isolates were collected from 18 hospitals across China. Minimum inhibitory concentrations were determined by CLSI broth microdilution and interpreted according to CLSI M100 (2021) guidelines. In addition, organ-specific weighted incidence antibiograms (OSWIAs) were constructed.
RESULTS
Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) were the most common pathogens isolated from BSI, IAI and UTI, accounting for 80% of the Gram-negative clinical isolates, while Pseudomonas aeruginosa (P. aeruginosa) was mainly isolated from RTI. E. coli showed < 10% resistance rates to amikacin, colistin, ertapenem, imipenem, meropenem and piperacillin/tazobactam. K. pneumoniae exhibited low resistance rates only to colistin (6.4%) and amikacin (17.5%) with resistance rates of 25-29% to carbapenems. P. aeruginosa exhibited low resistance rates only to amikacin (13.4%), colistin (11.6%), and tobramycin (10.8%) with over 30% resistance to all traditional antipseudomonal antimicrobials including ceftazidime, cefepime, carbapenems and levofloxacin. OSWIAs were different at different infection sites. Among them, the susceptibility of RTI to conventional antibiotics was lower than for IAI, UTI or BSI.
CONCLUSIONS
Gram-negative bacteria collected from Chinese EDs exhibited high resistance to commonly used antibiotics. Susceptibilities were organ specific for different infection sites, knowledge which will be useful for guiding empirical therapies in the clinic.
Topics: Humans; China; Anti-Bacterial Agents; Microbial Sensitivity Tests; Gram-Negative Bacteria; Emergency Service, Hospital; Gram-Negative Bacterial Infections; Urinary Tract Infections; Respiratory Tract Infections; Intraabdominal Infections; Drug Resistance, Bacterial; Female; Male
PubMed: 38760687
DOI: 10.1186/s12879-024-09294-0 -
BMC Microbiology May 2024We aimed to compare the performance of carbapenemase classification in carbapenem-resistant Klebsiella pneumoniae (CRKP) obtained using the BD Phoenix CPO Detect panel... (Comparative Study)
Comparative Study
BACKGROUND
We aimed to compare the performance of carbapenemase classification in carbapenem-resistant Klebsiella pneumoniae (CRKP) obtained using the BD Phoenix CPO Detect panel (CPO panel) and Cepheid Xpert Carba-R assays. We analyzed 55 CRKP strains from clinical specimens collected between November 2020 and November 2022. The CPO panel was used to detect both antibiotic susceptibility and phenotypic carbapenemase classes, while Xpert Carba-R was employed to identify KPC, NDM, VIM, OXA-48, and IMP genes. Due to the limited availability of molecular kits, we arbitrarily selected 55 isolates, identified as carbapenemase-producing according to the CPO panel and with meropenem minimum inhibitory concentration values > 8 mg/L.
RESULTS
According to the Xpert Carba-R assay, 16 of the 55 isolates (29.1%) were categorised as Ambler Class A (11 of which matched CPO panel Class A identification); three isolates (5.5%) were identified as Class B and 27 isolates (49.1%) as Class D (in both cases consistent with CPO panel B and D classifications). A further eight isolates (14.5%) exhibited multiple carbapenemase enzymes and were designated as dual-carbapenemase producers, while one isolate (1.8%) was identified as a non-carbapenemase-producer. The CPO panel demonstrated positive and negative percent agreements of 100% and 85.7% for Ambler Class A, 100% and 100% for Class B, and 96.4% and 100% for Class D carbapenemase detection, respectively.
CONCLUSION
While the CPO panel's phenotypic performance was satisfactory in detecting Class B and D carbapenemases, additional confirmatory testing may be necessary for Class A carbapenemases as part of routine laboratory procedures.
Topics: beta-Lactamases; Klebsiella pneumoniae; Bacterial Proteins; Humans; Microbial Sensitivity Tests; Klebsiella Infections; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae
PubMed: 38760674
DOI: 10.1186/s12866-024-03311-7 -
The Lancet Regional Health. Southeast... Jul 2024Antimicrobial resistance (AMR) has escalated to pandemic levels, posing a significant global health threat. This study examines the patterns and trends of AMR in...
BACKGROUND
Antimicrobial resistance (AMR) has escalated to pandemic levels, posing a significant global health threat. This study examines the patterns and trends of AMR in Bloodstream Infections (BSIs) across India, aiming to inform better surveillance and intervention strategies.
METHODS
Six-year data from 21 tertiary care centers in the Indian Council of Medical Research's AMR Surveillance Network (IAMRSN) were retrospectively analyzed to estimate cluster-robust trends in resistance. Time-series analysis was used to discern lead/lag relationships between antibiotic pairs and the directional influence of resistance in community and hospital-acquired BSIs(CA/HA BSIs). A data-driven Bayesian network ensemble averaged over 301 bootstrap samples was modelled to uncover systemic associations between AMR and Sustainable Development Goals (SDGs).
FINDINGS
Our findings indicate significant (p < 0.001) monthly increases in Imipenem and Meropenem resistance for , , and BSIs. Importantly, Carbapenem resistance in HA-BSIs preceded that in CA-BSIs for and (p < 0.05). At a national level, Cefotaxime resistance emerged as a potential early indicator for emerging Carbapenem resistance, proposing a novel surveillance marker. In BSIs, states with higher achievement of SDG3 goals showed lower Imipenem resistance. A model-based AMR scorecard is introduced for focused interventions and continuous monitoring.
INTERPRETATION
The identified spatiotemporal trends and drug resistance associations offer critical insights for AMR surveillance aligning with WHO GLASS standards.The escalation of carbapenem resistance in BSIs demands vigilant monitoring and may be crucial for achieving SDGs by 2030. Implementing the proposed framework for data-driven evidence can help nations achieve proactive AMR surveillance.
FUNDING
No specific funding was received for this analysis.
PubMed: 38757091
DOI: 10.1016/j.lansea.2024.100412 -
Cureus Apr 2024Black hairy tongue (BHT) is a lesion in which the filiform papillae of the tongue are significantly extended by hyperkeratosis, thereby giving the tongue a hairy...
Black hairy tongue (BHT) is a lesion in which the filiform papillae of the tongue are significantly extended by hyperkeratosis, thereby giving the tongue a hairy appearance. Here, we report two rare cases of children with BHT and tooth discoloration caused by antimicrobial agents. Case 1: A four-year-old female patient received intravenous linezolid after spinal surgery, and BHT developed on day eight of treatment. Subsequently, the patient developed teeth discoloration. Linezolid was continually administered for 50 days, and BHT and teeth discoloration improved 10 days after the end of linezolid treatment. Case 2: A two-year-old male patient with a brain abscess received intravenous meropenem and vancomycin. On the fourth day of treatment, BHT developed, and teeth discoloration was subsequently observed. Antibiotic therapy was continued for 82 days, and BHT and tooth discoloration improved 20 days after the treatment was discontinued.
PubMed: 38756316
DOI: 10.7759/cureus.58354